Gene expression is very accurate because the enzymes involved play an active role in selecting the correct counterpart for template information through a mechanism of proofreading. I propose to isolate and characterize biochemically E. coli mutants altered in accuracy of gene expression. Non-lethal mutants affecting the ribosome or RNApolymerase will be selected directly by their inability to efficiently propagate certain bacteriophages. Altered levels of transcription and mistranslation can be monitored in vivo by including a sensitive dye for lactose operon expression. In particular, mutants with altered release factors, elongation factor Tu-Ts, 30S ribosomal protein S1, RNApolymerase subunits and possibly sigma factor are expected among the candidates. It is likely that alteration of cell components involved in maintaining accuracy of gene expression will have far reaching consequences for cell physiology. A better understanding of these mechanisms in E. coli will be helpful in evaluating their possible role in eukaryotic cells, particularly with respect to aging and cancer.